VAP-1 is an amine oxidase (semicarbazide-sensitive amine oxidase, SSAO) which is abundant in human plasma (Non-Patent Document 1), and shows remarkably increased expression in vascular endothelium and vascular smooth muscle of inflammatory regions. While the physiological role of VAP-1 has not been clarified until recently, VAP-1 gene was cloned in 1998, and VAP-1 has been reported to be a membrane protein that regulates rolling and migration of lymphocytes and NK cells as an adhesion molecule under regulation of expression by inflammatory cytokines. Although the amine acting as a substrate is unknown, it is considered to be methylamine generated in any part of a living body. It is also known that hydrogen peroxide and aldehydes produced due to the amine oxidase activity in the molecule are important factors of adhesion activity.
A recent report has demonstrated that the VAP-1 enzyme activity in plasma increases in patients with diabetes mellitus, whether type I or type II, and the increase is particularly remarkable in patients with diabetes mellitus suffering from retinopathy complications (Non-Patent Documents 2 and 3).
In addition, it has been reported that VAP-1 is related to the following diseases:
(1) cirrhosis, essential stabilized hypertension, diabetes mellitus, and arthrosis (Patent Documents 1 and 2);
(2) endothelium damage (in diabetes mellitus, arterosclerosis, and hypertension), cardiovascular diseases related to diabetes mellitus and uremia, pain related to gout and arthritis, and retinopathy (in diabetes mellitus patients) (Patent Document 3);
(3) inflammatory diseases or conditions (of connective tissue) (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and osteoarthritis or degenerative joint disease, Reiter's syndrome, Sjogren's syndrome, Behcet's syndrome, relapsing polychondritis, systemic lupus erythematosus, discoid lupus erythematosus, systemic sclerosis, eosinophilic fasciitis, polymyositis, dermatomyositis, polymyalgia rheumatica, vasculitis, temporal arteritis, polyarteritis nodosa, Wegener's granulomatosis, mixed connective tissue disease, and juvenile rheumatoid arthritis); gastrointestinal inflammatory diseases or conditions [Crohn's disease, ulcerative colitis, irritable bowel syndrome (spastic colon), fibrotic conditions of the liver, inflammation of the oral mucosa (stomatitis), and recurrent aphtous stomatitis]; central nervous system inflammatory diseases or conditions (multiple sclerosis, Alzheimer's disease, and ischemia-reperfusion injury related to ischemic stroke); pulmonary inflammatory diseases or conditions (asthma, adult respiratory distress syndrome, and chronic obstructive pulmonary disease); (chronic) skin inflammatory diseases or conditions (psoriasis, allergic lesions, lichen planus, pityriasis rosea, contact dermatitis, atopic dermatitis, and pityriasis rubra pilaris); diseases related to carbohydrate metabolism (diabetes mellitus and complications from diabetes mellitus) including microvascular and macrovascular diseases (arterosclerosis, vascular retinopathies, retinopathy, nephropathy, nephrotic syndrome and neuropathy (polyneuropathy, mononeuropathies and autonomic neuropathy), foot ulcers, joint problems, and increased risk of infection); diseases related to aberrations in adipocyte differentiation or function or smooth muscle cell function (arterosclerosis and obesity); vascular diseases [atheromatous arterosclerosis, nonatheromatous arterosclerosis, ischemic heart disease including myocardial infarction and peripheral arterial occlusion, Raynaud's disease and phenomenon, and thromboangiitis obliterans (Buerger's disease)]; chronic arthritis; inflammatory bowel diseases; and skin dermatoses (Patent Documents 4, 5, and 6, and Non-Patent Documents 4 and 5);
(4) diabetes mellitus (Patent Document 7);
(5) SSAO-mediated complications [diabetes mellitus (insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM)) and vascular complications (heart attack, angina, strokes, amputations, blindness, and renal insufficiency)], and macular edema (for example, diabetic and non-diabetic macular edema) (Patent Documents 8 and 9); and
(6) hepatitis, transplantation, and the like.
Accordingly, the compounds acting on a VAP-1 enzyme may be used as an agent for preventing and/or treating the above-described diseases.
On the other hand, in Patent Document 9, it is disclosed that a compound represented by the formula (A) has a VAP-1 inhibitory activity.

(wherein Z represents

For the other symbols in the formula, refer to the corresponding patent publications)
Further, in Patent Document 10, it is disclosed that a compound represented by the formula (B) has a VAP-1 inhibitory activity.

(For the symbols in the formula, refer to the corresponding patent publications)
In Patent Document 11, it is disclosed that a compound represented by the formula (C) has a VAP-1 inhibitory activity and is effective in applications for treatment of VAP-1-related diseases, in particular, macular edema.

(wherein Z represents

For the other symbols in the formula, refer to the corresponding patent publications)
In addition, in Patent Document 12, it is disclosed that a compound represented by the formula (D) has a VAP-1 inhibitory activity.

(wherein
D represents —NR3 and E represents amino which may be substituted (optionally substituted amino), for the other symbols, refer to the corresponding patent publications)
In Patent Document 13, it is disclosed that a compound represented by the formula (E) has a VAP-1 inhibitory activity.

(wherein
X represents a divalent residue derived from thiazole which may be substituted (divalent residue derived from optionally substituted thiazole),
Z represents A-B-D-E, A represents a divalent residue derived from benzene which may be substituted (divalent residue derived from optionally substituted benzene) or a divalent residue derived from thiophene which may be substituted (divalent residue derived from optionally substituted thiophene), B represents —(CH2)1—NR2—CO—, D represents —NR3, and E represents amino which may be substituted (optionally substituted amino), for the other symbols, refer to the corresponding patent publications)
In Patent Document 14, it is disclosed that a compound represented by the formula (F) has a GPR119 agonistic activity, and is thus useful for, for example, treatment of diabetes mellitus or the like.

(For the symbols in the formula, refer to the corresponding patent publications)
In Patent Document 15, it is disclosed that a compound represented by the formula (G) has a GPR119 agonistic activity, and is thus useful for, for example, treatment of diabetes mellitus or the like.

(For the symbols in the formula, refer to the corresponding patent publications)
In Patent Document 16, which is a patent application published after the filing date of the application which forms the basis of the priority of the present application, it is disclosed that a compound represented by the formula (H) has a VAP-1 activity.
